Carole L Wallis1, Michael D Hughes2, Justin Ritz2, Raquel Viana1, Carlos Silva de Jesus3, Shanmugam Saravanan4, Marije van Schalkwyk5, Rosie Mngqibisa6, Robert Salata7, Peter Mugyenyi8, Evelyn Hogg9, Laura Hovind10, Linda Wieclaw10, Robert Gross11, Catherine Godfrey12, Ann C Collier13, Beatriz Grinsztejn3, John W Mellors14. 1. Bio Analytical Research Corporation South Africa and Lancet Laboratories, Johannesburg, South Africa. 2. Harvard TH Chan School of Public Health, Boston, Massachusetts, USA. 3. Instituto Nacional de Infectologia Evandro Chagas, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. 4. Y.R. Gaitonde Centre for AIDS Research and Education, Chennai, India. 5. Family Clinical Research Unit Clinical Research Site, Stellenbosch University, Cape Town, South Africa. 6. Durban Adult Human Immunodeficiency Virus Clinical Research Site, Enhancing Care Foundation, Durban, South Africa. 7. Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. 8. Joint Clinical Research Center, Kampala, Uganda. 9. Social and Scientific Systems, Inc, Silver Spring, Maryland, USA. 10. Frontier Science & Technology Research Foundation, Amherst, New York, USA. 11. University of Pennsylvania, Philadelphia, Pennsylvania, USA. 12. Division of Acquired Immunodeficiency Syndrome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 13. University of Washington School of Medicine, Seattle, Washington, USA. 14. Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Abstract
BACKGROUND: Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC). METHODS: Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated. RESULTS: Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients. CONCLUSIONS: Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.
BACKGROUND: Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC). METHODS: Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated. RESULTS: Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients. CONCLUSIONS: Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.
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